.. -. U. SPONDYLOMETAPHYSEAL DYSPL.ASIA

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1 Spondylometaphyseal Dysplasia A family is described in which the father, son, and daughter have spondylometaphyseal dysplasia, consistent with an autosomal dominant pattern of inheritance. Radiologic changes spanning a period from 4 months to 31 years are described. Platyspondyly and metaphyseal deformity predominate. The severity of the radiologic changes is variable. In 1967, Kozlowski et al. [1] delineated a distinct shorttrunk type of dwarfism with vertebral and metaphyseal dysplasia, termed spondylometaphyseal dysplasia. Since then, a number of cases have been reported, mainly in the European literature [2-7]. While the disorder is probably not rare, it has received little attention until recently. ii: This paper describes spondylometaphyseal dysplasia in a father and his son and daughter. The radiographic features oven a period of 4 months to 31 years show the evolution of the bone changes. 2 Family History The proband, a 29-year-old man with spondylometaphyseal dysplasia (fig. 1, IV-1), was referred to the genetic I 0 MALE 0 FEMALE U. SPONDYLOMETAPHYSEAL DYSPL.ASIA 4, PROPOSITUS Fig. 1.-Family pedigree. P. 5. THOMAS AND N. C. NEVIN2 % DECEASED IJ EXAMINED ACHONDROPLASIA counseling clinic in 1972 for evaluation of the risk of transmitting his skeletal abnormality to his unborn child. He had had a spinal curvature and a waddling gait since he was 2. Clinical examination revealed dwarfism of the short-trunk variety; height was 133 cm (fig. 2A). The head and face were normal. The neck was short and he had a kyphoscoliosis. There was slight joint limitation at the elbows, hips, and knees. The hands were normal but the wrists were broad. Intelligence was normal. The proband s father and mother (Ill-i and 111-2) were 180 and 170 cm tall, respectively. They were not related. A maternal second cousin (IV-7) had achondroplasia. No other relative had a skeletal abnormality. A paternal first cousin of the patient and a maternal first cousin of his wife each had a hare lip. A nephew had spina bifida and hydrocephalus. The proband s son (V-i ) was born in October 1972 after 42 weeks of gestation. He had no obvious clinical abnormalities. Because of the history of dwarfism in the father, a spinal x-ray was taken at 8 months. At 14 months of age he walked with a waddling gait. The head and face were I B 3f M :,.. -. Fig. 2 -Photograph offather (age 31) and son (11/2 years) with spondylometaphyseal dysplasia --- Received January ; accepted after revision July Department of Radiology. Royal Belfast Hospital for Sick Children. Belfast. Northern Ireland 2 Department of Medical Genetics, Queen s University of Belfast, Belfast, Northern Ireland. Am J Roentgenol 128:89-93, January

2 .,....; 90 THOMAS AND NEVIN normal. Elbow and knee extension was slightly limited. Height was 72.5 cm (fig. 2B). Thede was also bowing of the legs and a mild degree of kyphosis. Intelligence was nonmal. The daughter (V-2) was born in May 1974, after 41 weeks of gestation. She had a left hare lip and large cleft palate defect. Again, because of the family history a full skeletal survey was carried out. Serum calcium and phosphorus, screening for urinary mucopolysacchanides, urinary aminoacid chromatogram, and cytogenetic analysis were normal in all three patients. Radiographic Findings Two skeletal surveys were available on each patient, documenting changes between the ages of 4 months and 31 years. Spine The main features were platyspondyly, increased disc spaces, anterior tapering of the vertebral bodies, and kyphoscoliosis. Platyspondyly was maximal in infancy (fig. 3A ) when the width of the disc spaces was greaten than the height of the vertebral bodies; it became less evident with increasing age. It was most pronounced in the cervical region (fig. 38). Anterior tapering was not present before 1 year of age, progressed in childhood, and involved the lower dorsal vertebrae (fig. 4A). A scoliosis was first seen at the dorsolumbar junction at the age of 2 years and thereafter progressed with age (fig. 4B). Kyphosis in the upper dorsal region developed later. Pelvis The pelvis appeared normal at 4 months of age. By 8 months slight broadening of the bases of the iliac bones was apparent, and the acetabular roofs were flat (fig. 5). The shape of the pelvis did not alter materially in childhood, but undendevelopment of the femoral necks became more obvious. The adult pelvis had square iliac wings and marked coxa vara, so that the greater trochanters almost touched the anterior iliac spines (fig. 6). Long Bones The main features were metaphyseal broadening and irregularity involving particularly the lower limbs (fig. 7). In infancy the length of the long bones was normal

3 SPONDYLOMETAPHYSEAL DYSPLASIA 91 Fig. 4.-Spinal radiographs of father. A. Lateral dorsal spine at 6 years. B. AP dorsolumbar spine at 6 years but became shorter relative to normal standards as growth progressed. The growth plates of the lower femona and upper tibiae at 2 years were oblique with lateral bowing of the tibial shafts, but in case 1 the knees appeared normal at 6 years of age. Hands and Feet There was delay in appearance of the ossification centers of the carpus and tarsus in infancy and childhood with slight irregularity of the metaphyses of the short tubular bones. Later development was normal. Bone age in infancy and childhood was retarded. Skull No abnormality was visible at any age. Discussion Spondylometaphyseal dysplasia was delineated as a distinct entity by Kozlowski et al. [1]. Since their three cases were sporadic, they concluded that the condition was inherited as an autosomal recessive trait. However, Refior [2] described spondylometaphyseal in a father, son, and daughter and suggested autosomal dominant inheritance. This interpretation was subsequently supported by Michel et al. [4] and Riggs and Summitt [6]. More recently, a family has been described with an affected father and son [7]. The pattern in our family is consistent with autosomal dominant inheritance. Thus five families with spondylometaphyseal dysplasia, three showing male-to-male transmission, have now been reported with autosomal dominant inheritance. The characteristic radiologic changes have been Fig. 5.-Pelvis of daughter at 1 year.

4 92 THOMAS AND NEVIN Fig. 7.-Lower limb of son at 2 years. Fig. 6.-Pelvis of father at 31 years. clearly defined so that the diagnosis should no longer present serious problems, even in adult patients. The variation in severity of these changes and their relationship to age have not yet been fully determined. The major findings in the spine are platyspondyly and kyphosis which become more severe with increasing age. Scoliosis is frequently present. A scoliosis is already developing at the dorsolumbar junction in the son at 2 years of age. In the father scoliosis was mild at 6 years of age but severe in adulthood, contributing significantly to loss of stature. Shortening of the femoral necks and coxa vana are characteristic findings. In our three cases these changes are severe. Variability in the degree of involvement of other metaphyses may also be present. Changes in the knee in childhood have been described. In the son and daughter severe metaphyseal changes at the knee were present in infancy, whereas in the father the knees were virtually normal at 6 years of age. Reduction in the length of the long tubular bones was not present in early infancy and, although becoming apparent later, was never severe. Although spondylometaphyseal dysplasia is a distinct entity, clinically and radiologically, variants may exist. Mundoch and Walker [8] described a new form of spondylometaphyseal dysplasia characterized by disproportionate dwarfism evident at birth, deformity of chest, spine, and limbs, loose jointedness, and marked pes planus. The radiologic changes were bulbous enlargement of the long bone metaphyses with small oval radiolucent areas with sclerotic borders and moderate

5 SPONDYLOMETAPHYSEAL DYSPLASIA 93 to severe platyspondyly. They mentioned three other patients with this form of spondylometaphyseal dysplasia [8]. McKusick [9] has also observed a type of spondylometaphyseal dysplasia, the Strudwick form or spondylometaphyseal dysplasia congenita. In addition to the skeletal dysplasia, the patients have a cleft palate, myopia, and atlantoaxial instability. In early life radiologic changes are indistinguishable from spondyloepiphyseal dysplasia but in later life are characteristic of spondlylometaphyseal dysplasia. A striking feature of this form is the dappled epiphyses. Since the six cases are sporadic, this form may also be inherited as an autosomal dominant [9]. In our family, the daughter had a hare lip and cleft palate in addition to the skeletal dysplasia. This association has been described in congenital spondyloepiphyseal dysplasia [10] and in variants of spondylometaphyseal dysplasia [7, 8]. However, because there is a family history of hare lip and cleft palate, this may be a chance association. It is hoped that further observation of patients with spondylometaphyseal dysplasia will show whether orthopedic management can prevent the development of the kyphoscoliosis and if there is a relationship between the severity of the metaphyseal changes in childhood and the development of arthritis in adult life. ACKNOWLEDGM ENTS We thank Dr. 0. Woods for referring this family and the Department of Medical Photography for preparing the illustrations. REFERENCES 1. Kozlowski K, Maroteaux P. Sprangen J: La dysostose spondylo-m#{233}taphysaire. Presse Med 75: , Refion HJ: Zur spondylo-metaphysaren dysostose. Typ Kozlowski-M anoteaux-spnanger. A rch Orthop Unfallchin 66: , Remy J, Nuyto J-P, Bombart E, Rembent A: La dysostose spondylo-m#{233}taphysaire. A propos de deux observations. Ann Radiol (Paris) 13: , Michel J, Grenier B, Castaing J, Augien JL, Desbuquois G: Deux case familaux de dysplasie spondylo-m#{233}taphysaine. Ann Radiol ( Paris) 1 3 : , Piffaretti PG. Delgado H, Nussle D: La dysostose spondylo-metaphysaire de Kozlowski, Maroteaux et Lamy. Ann Radio! (Paris) 13: , Riggs W, Summitt RL: Spondylometaphyseal dysplasia (Kozlowski): Report of an affected mother and son. Radiology 101: , LeQuesne GW, Kozlowski K: Spondylometaphyseal dysplasia. Br J Radiol 46: , Mundoch JL, Walker BA: A new form of syondylometaphyseal dysplasia: Birth Defects: Onig Ant Sen 5(4): , McKusick VA: Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive and X- linked Phenotypes, 4th ed. Baltimore, Johns Hopkins University Press, Canter CO. Fairbank TJ: The Genetics of Locomotor Disorders. London, Oxford University Press, 1974

6 This article has been cited by: 1. H. B. Diren, B. Büyükgebiz, A. Büyükgebiz, T. Pirnar Spondylometaphyseal dysplasia, type VII. Pediatric Radiology 22:2, [Crossref] 2. A. Bagga, R. N. Srivastava, S. Gupta, A. Gupta Spondylometaphyseal dysplasia with hypercalcemia. Pediatric Radiology 19:8, [Crossref] 3. K. -H. Gustavson, G. Holmgren, F. Probst Spondylometaphyseal dysplasia in two sibs of normal parents. Pediatric Radiology 7:2, [Crossref] 4.. Spondylometaphyseal Dysplasia, Kozlowski Type [Crossref]